A patch-clamp method in electrophysiology is known as the “gold standard” method for measuring ion channel activity in cell membrane. Ion channels have crucial roles in physiology and pathophysiology and are important drug targets. Patch clamping has rapidly become the “gold standard” in studying ion channel function but is still a laborious process requiring precision micromanipulation under high power visual magnification, vibration dumping, and an experienced and skilful experimenter, thus having been judged unfavorable for high throughput recording. In recent developments, the application of microstructured chips for patch clamping has been put forward, the common patch pipette is replaced by a microfabricated chip that enable the positioning and sealing of cells via an automated suction protocols.
Planar probes utilizing processing technologies are proposed. Such probes are applicable to an automated system which does not require the inserting of a micro pipette into a cell.
Japanese Patent Laid-Open Publication No. 2003-527581 discloses a device for electrically measuring an object in a medium. In this device, the object seals an orifice, thereby providing first and second cavities insulated electrically from each other. Then, the device measures the object electrically in the medium based on an impedance between electrodes located in the first and second cavities, respectively.
International Application Publication No. WO02/055653 discloses a technique of measuring an extracellular potential with a cell electro-physiological sensor which includes wells provided in a substrate with cell holders, measuring electrodes for measuring an electrical signal at each well, and reference electrodes.
“Micro Total Analysis Systems 2004”, pp. 521-522, T. Sordel et al (2004) discloses a technology for tightly holding an HEK293 cell, which is a human cultured cell in a hole having a diameter of 2.5 μm in a layer made of SiO2, and for measuring an extracellular potential.
A through-hole provided in a planar substrate functions as a tip opening of a glass pipette. This hole allows electro-physiological phenomenon of cells to be recorded precisely while the cells are automatically pulled and easily held by a suction force from a back surface of the substrate. It is important for the measuring of the cells with a small background noise that the cells are securely held in the planar substrate of a device.
However, none of the above prior arts describes an optimum structure of the planar substrate, such as its shape and its surface condition, which affects holding properties of the cells.